Our research efforts are directed toward investigating the effect and mode of action of hormones and xenobiotics on the regulation of enzyme patterns during perinatal development. Particular emphasis has been placed on the postnatal development of hepatic enzymes in the rat following perinatal exposure to gonadal hormones (testosterone propionate (TP) or estradial-17-beta(E2) ) and hormonally active xenobiotics (polychlorinated biphenyl (PCB), diethylstilbestrol (DES), dichloro-diphenyl-trichloro-ethane (DDT) and methoxychlor). We have investigated the altered ontogeny and sex differentiation of several hepatic enzyme markers following prenatal exposure to the above mentioned chemical and the results of our studies on the role of the hypothalamic-pituitary-gonadal axis on the regulation of some of these enzymes. These studies have demonstrated that the regulation of hepatic enzyme development is different for different groups of enzymes and that the critical period for neonatal imprinting of enzyme activity is not the same for all enzymes. Further studies are investigating altered sex differentiation of hepatic enzymes by mapping protein profiles on 2-D gels.